Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft

Michael A. Turner, Hannah M. Hollandsworth, Hiroto Nishino, Siamak Amirfakhri, Thinzar M. Lwin, Andrew M. Lowy, Sukhwinder Kaur, Gopalakrishnan Natarajan, Kavita Mallya, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model. Materials and Methods: MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously. Results: In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465). Conclusion: MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.

Original languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalIn Vivo
Volume36
Issue number1
DOIs
StatePublished - Feb 2022

Keywords

  • Antibody
  • Fluorescence guided surgery
  • MUC5AC
  • Mucin
  • PDOX
  • Pancreatic cancer
  • Tumor-specific imaging

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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